Patients with stage IV gastric cancer have cancer that invades adjacent structures and lymph nodes or has spread to distant sites.

A variety of factors ultimately influence a patient's decision to receive treatment of cancer. The purpose of receiving cancer treatment may be to improve symptoms through local control of the cancer, increase a patient's chance of cure, or prolong a patient's survival. The potential benefits of receiving cancer treatment must be carefully balanced with the potential risks of receiving cancer treatment.

The following is a general overview of the treatment of stage IV gastric cancer. Circumstances unique to your situation and prognostic factors of your cancer may ultimately influence how these general treatment principles are applied. The information on this Web site is intended to help educate you about your treatment options and to facilitate a mutual or shared decision-making process with your treating cancer physician.

Most new treatments are developed in clinical trials. Clinical trials are studies that evaluate the effectiveness of new drugs or treatment strategies. The development of more effective cancer treatments requires that new and innovative therapies be evaluated with cancer patients. Participation in a clinical trial may offer access to better treatments and advance the existing knowledge about treatment of this cancer. Clinical trials are available for most stages of cancer. Patients who are interested in participating in a clinical trial should discuss the risks and benefits of clinical trials with their physician. To ensure that you are receiving the optimal treatment of your cancer, it is important to stay informed and follow the cancer news in order to learn about new treatments and the results of clinical trials.

Optimal treatment for some patients with stage IV gastric cancer often requires more than one therapeutic approach. Thus, it is important for patients to be treated at a medical center that can offer multi-modality treatment involving medical oncologists, radiation oncologists, surgeons, gastroenterologists and nutritionists.

Surgery Alone as Primary Treatment

In general, surgery alone is not usually advised for patients with stage IV gastric cancer except for palliation. Most patients with stage IV gastric cancer are treated with a combination of surgery, chemotherapy and/or radiation therapy. Patients with stage IV gastric cancer should consider treatment at a medical center with a surgical team that has experience and treats a large number of patients with gastric cancer each year. In one large clinical study that involved over 50,000 patients with all stages of gastric cancer treated between 1985 and 1996 in many different medical centers, the 5 and 10-year survival rates for patients with stage IV cancer were 7% and 5%, respectively. In general, patients who survived 5 years following treatment of stage IV gastric cancer had cancer that was completely removed with surgery.

Adjuvant Therapy (Treatment after surgery)

It is important to understand that some patients with gastric cancer already have small amounts of cancer that have spread into the lymph nodes and cannot be detected with any of the currently available tests. Undetectable areas of cancer are referred to as micrometastases. It is the presence of micrometastases that causes cancer recurrence following treatment with surgery alone. An effective treatment is needed to cleanse the body of micrometastases in order to improve a patient's duration of survival and potential for a cure. The delivery of cancer treatment following local treatment with surgery is referred to as adjuvant therapy and may include chemotherapy, radiation therapy and/or biologic therapy.

Several clinical trials have suggested that chemotherapy administered after surgery may prevent some cancer recurrences; however results from other clinical trials have not shown this effect. In order to determine the effectiveness of chemotherapy after surgery in preventing recurrences, doctors in Canada analyzed results from 13 major clinical trials that compared adjuvant chemotherapy treatment to no additional treatment following surgery for gastric cancer. They found a modest benefit for patients treated with adjuvant chemotherapy. The results indicated that 65% of patients treated with surgery alone experienced a recurrence and died, compared to approximately 61% of patients receiving adjuvant chemotherapy. The greatest benefit appeared to be in patients treated with more modern chemotherapy drugs. Over the past few years, several new chemotherapy drugs have been developed that appear to have more anti-cancer activity and are being evaluated in clinical trials.

Results from a large multi-institutional clinical study also indicate that adjuvant therapy significantly improves survival for patients with gastric cancer and should become the standard of care for this disease. The trial involved over 500 patients with gastric cancer who received surgery alone or surgery plus a combination of chemotherapy and radiation. All patients in the study underwent surgery to remove their cancer and had no evidence of cancer remaining following the surgical procedure. Half of the patients then received adjuvant combination chemotherapy consisting of 5-FU and leucovorin plus radiation. Three years following therapy, 50% of patients treated with surgery followed by adjuvant chemotherapy and radiation survived, compared with only 41% of patients treated with surgery alone. Three years following treatment, 48% of patients treated with adjuvant therapy survived without a cancer recurrence, compared to only 31% treated with surgery alone. The average duration of survival following surgery was 27 months, compared with 36 months for patients receiving surgery and adjuvant therapy.

Another clinical trial evaluated adjuvant chemotherapy without radiation in gastric cancer patients. All patients in this trial had cancer that had spread to nearby lymph nodes and were eligible for curative surgery. Half of the patients received combination chemotherapy consisting of epidoxorubicin, leucovorin and 5-fluorouracil for 7 months following surgery while the other half of patients received no adjuvant therapy (control group). Five years following therapy, 30% of the patients receiving adjuvant chemotherapy were still alive, compared with only 13% from the control group. The average survival time following treatment was 31 months for patients receiving adjuvant chemotherapy and only 18 months for the control group.

Results from both of these clinical trials are consistent with previous studies indicating that adjuvant therapy improves outcomes for patients with gastric cancer. The researchers in these studies have concluded that surgery following adjuvant therapy for stage I to IV gastric cancer reduces cancer recurrences and improves overall survival compared with surgery alone. Adjuvant therapy is considered the standard treatment for patients with gastric cancer for whom all detectable cancer can first be removed by surgery.

Neoadjuvant Therapy (Treatment given before surgery)

The practice of administering chemotherapy and/or radiation therapy before surgery is referred to as neoadjuvant therapy. In theory, neoadjuvant therapy can decrease the size of the cancer, thereby making it easier to remove with surgery. The major problems with this approach are the higher mortality rates that occur when radiation therapy and/or chemotherapy are administered before surgery and the delay of surgery for some patients who do not respond to therapy. In most but not all clinical studies chemotherapy, radiation therapy or both given before surgery have not improved survival following surgery in patients with stage IV gastric cancer. This may be related to the ineffectiveness of the drug combinations tested, which include various combination of 5-FU, doxorubicin and methotrexate. Many current clinical trials are directed at improving outcomes of patients with stage IV gastric cancer by administering newer neoadjuvant treatment regimens containing taxane or other newer chemotherapy agents and/or radiation therapy.

Combination Therapy as Primary treatment

Chemotherapy administered with or without radiation therapy is the main treatment for patients with stage IV gastric cancer that cannot be completely removed with surgery. Single chemotherapy agents such as Platinol®, 5-FU, Mutamycin®, doxorubicin, and Ellence® have been used for the treatment of stage IV gastric cancer for several years. However, these drugs result in clinical responses in less than half of patients with stage IV gastric cancer and virtually no complete responses are seen following single agent chemotherapy. Survival of patients treated with 5-FU-based chemotherapy combinations is less than one year from diagnosis. Recent clinical trials indicate that newer chemotherapy agents such as Camptosar®, Gemzar® , Taxotere® and paclitaxel may be the most active single agents for the treatment of gastric cancer. Current clinical trials are evaluating various combinations of these newer drugs, often in combination with Platinol® and fluorouracil.

Two separate clinical trials conducted in Europe evaluated the combination of Taxotere® and Platinol® in patients with locally advanced and metastatic gastric cancer. Overall anti-cancer response rates ranged from 37% to 56% and the average survival duration was approximately 9 to 10 months. Higher doses of Taxotere® resulted in improved treatment outcomes.

Researchers from Italy conducted another clinical trial evaluating Taxotere® as a single agent following the chemotherapy combination consisting of Platinol®, Ellence®, 5-FU and leucovorin (PELF) in patients with locally advanced and metastatic gastric cancer. The overall anti-cancer response rate following PELF was 40% which was improved to almost 58% after Taxotere® administration. This is nearly a 50% increase in anti-cancer responses with the addition of single agent Taxotere®.

In another clinical trial, 25 patients with gastric or gastroesophageal cancer were treated with the combination of paclitaxel, Platinol® and etoposide. Eighteen patients had locally advanced cancer and 7 had spread of cancer to the liver. All patients responded to treatment, with a 50% or greater reduction in the size of their cancer and 3 patients experienced a complete disappearance of their cancer. It was concluded from this clinical trial that the combination of paclitaxel, Platinol® and etoposide was very active for the treatment of gastric and gastroesophageal cancer.

Paclitaxel has been given concurrently with radiation therapy for the treatment of gastric cancer. In one reported clinical trial, 27 patients with inoperable gastric cancer were treated with paclitaxel and concurrent radiation therapy. The overall anti-cancer response rate was 56%, including 11% with a complete response. At two years from initiation of treatment, 29% of patients survived without progression of their cancer. The combination of paclitaxel and radiation therapy demonstrates substantial activity for the local control of advanced gastric cancer. These and other clinical trials suggest that aggressive multi-modality treatment with chemotherapy, radiation therapy and surgery can be of benefit for patients with inoperable gastric cancer.

Strategies to Improve Treatment

The progress that has been made in the treatment of gastric cancer has resulted from the use of multi-modality treatment and improved patient and physician participation in clinical trials. Future progress in the treatment of gastric cancer will result from continued participation in appropriate trials. Currently, there are several areas of active exploration aimed at improving the treatment of gastric cancer.